This application describes plans at the University of Pennsylvania to train the next generation of outstanding independent investigators in patient-oriented researchers (POR). The NIH defines POR as research involving actual contact between the investigator and the volunteer participant, often conducted in patients in the setting of a General Clinical Research Center (GCRC). Despite the high profile and importance of this type of research, the past two decades have witnessed a serious decline in the number of superbly trained and motivated clinical researchers to design, conduct and analyze POR. Despite the marked increase in opportunity to perform such research and the need for investigators to facilitate translation of discoveries in basic research into clinical medicine, few formal training programs exist which foster expertise in POR. The need for training such investigators has been underscored recently by the reports of separate task forces from the NIH and the Institute of Medicine that were formed to examine and make recommendations for NIH training of clinical investigators. Clinical research has thrived at Penn in the last decade and the applicants already have a superb record of accomplishment in training clinical researchers. Furthermore, the development of an integrated training program in POR at the University of Pennsylvania has been facilitated by the awarding of a curriculum development award - the K30 award. The proposed Mentored Career Development in POR is designed to prepare and train clinicians for careers at the cutting edge of translational, clinical, and patient-oriented research. The specific training objectives for this program are: 1) Provide information in advances in basic molecular and cell biology specifically relevant to the candidate's clinical research interest; 2) Provide a series of didactic courses relevant to training in clinical research within the context of a Masters Degree Program in POR; 3) Train the candidate in the conduct of clinical research through the interaction with a lead mentor; 4) Provide training in biostatistics, epidemiology and clinical trials design sufficient for candidates to properly design and interpret their future clinical trials; 5) Ensure knowledge and understanding of ethical issues in clinical biomedical research; 6) Provide close mentoring of the candidates by experienced clinical researchers, to provide positive clinical research roles models in a supportive academic environment. The overall goal of this Program is to train future clinical researchers equipped with a sophisticated background in basic science and clinical research practice. It is envisioned that the clinical researchers will graduate this program at the leading edge of their research field, ideally positioned to launch novel and decisive clinical research studies and to compete for NIH funding for original and independent clinical research projects.